This project will examine in detail the factors which control development of site-specific function in the small intestine, utilizing a fetal intestine transplant model. Previous studies indicate that intrinsic factors predominate in directing the ontogeny of site-specific function and that extrinsic influences are subordinate. The morphological, ultrastructural, and biochemical differentiation of rat fetal intenstine transplanted at various stages of gestation will be investigated in order to determine the time of onset of site-specific function and whether or not there is a stage at which the intestine is pluripotent and regional differentiation is determined by extrinsic factors. This question will be further explored by studies of the development of isolated endoderm in the transplant system. Since preliminary results indicate significant differences between brush border proteins from transplant and control tissue, the effects of duodenal fluid and pancreatic proteases on the brush border proteins will also be examined to determine if this treatment will convert transplant to control patterns. A specific brush border protein, sucrase-isomaltase, will be isolated from transplant preparations and its characteristics compared to control sucrase-isomaltase to assess the role of intraluminal events in the activation or insertion of this protein into the brush border. This approach should yield a significant new understanding of the relative role of intrinsic and extrinsic factors in determining site-specific morphological and biochemical maturation in the mammalian small intestine and complement available data on the role of hormones in extrinsic regulation of intestinal maturation.